This is a revision of application 1 R01 HL079235-01. The overall goal of this project is to understand how depression leads to congestive heart failure (CHF) in older adults. Depression is known to be associated with an increased risk of coronary heart disease (CHD), and with adverse outcomes among older adults with CHD. Recent evidence suggests that depression is also associated with an increased risk of CHF, and with adverse outcomes among older adults with CHF. However, the mechanisms by which depression leads to CHF are not known. To determine the mechanisms of association between depression and CHF, we will use an existing cohort of 1024 older adults (mean age 67) with CHD (including 680 with no heart failure and 344 with clinical or subclinical heart failure) who were recruited between 9/00 and 12/02 for The Heart and Soul Study." The Heart and Soul Study was originally designed to understand the mechanism of association between depression and CHD. Since patients with CHD are at high risk for CHF, this well-characterized cohort will provide a unique opportunity to examine the relation between depression and CHF. At baseline, participants completed a depression interview (Diagnostic Interview Schedule); full exercise treadmill testing with stress echocardiography; 24-hour Holter monitoring for heart rate variability; 24-hour urine collection for cortisol and norepinephrine; venous blood measurements for lipids, platelet reactivity, and C-reactive protein; and an extensive questionnaire. Participants have been followed annually by telephone. We will invite all participants to return for a 5-year examination, and we will follow them for an additional 3 years thereafter, to determine (a) the independent association between baseline depression and CHF, and (b) the extent to which 5-vear changes in biological and behavioral factors associated with depression explain the relation between depression and CHF. By identifying the mechanisms that explain the relation between depression and CHF, this study will enable us to target specific areas for improving the treatment of these patients.